Methods and apparatuses for radiation treatment

ABSTRACT

Methods and apparatuses for positioning a radiation source in vivo relative to radio-opaque markers on a catheter that delineate a therapeutic treatment length so that a therapeutic dose of radiation is delivered along the therapeutic treatment length.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.60/155,507, filed Sep. 22, 1999.

FIELD OF THE INVENTION

The present invention relates to the field of intravascular radiationtherapy. In particular, the present invention relates to anintravascular radiation therapy to inhibit restenosis of a vessel.

DESCRIPTION OF RELATED ART

Coronary artery balloon angioplasty is a minimally invasive techniquedeveloped as an alternative to coronary artery bypass grafting fortreatment of atherosclerosis, the principle process of heart disease.There are about 450,000 coronary interventions, i.e., angioplasty,atherectomy, and stent procedures, performed annually in the U.S.However, a major limitation of this clinical procedure is the highprevalence of restenosis, or re-narrowing, of the treated vessel.Restenosis occurs approximately 30-50% of the time.

Restenosis occurs as a result of injury to the vessel wall due to theangioplasty procedure, or other procedures, such as stenting, and/oratherectomy. Restenosis is a complex process, which can involve animmediate vascular recoil, neointimal hyperplasia, and/or late vascularremodeling. Neointimal hyperplasia, a response of the body toballoon-induced physical injury of the vessel wall, is thought to be themain contributor to restenosis. Hyperplasia can result in narrowing ofthe vessel lumen within 3-6 months after angioplasty due toproliferation of smooth muscle cells in the region injured by theangioplasty. Restenosis can require the patient to undergo repeatangioplasty procedures or by-pass surgery with added costs and risks tothe patient.

One procedure currently used to inhibit restenosis involves delivery ofa prescribed dose of radiation to the injured portion of the vesselusing intravascular radiation therapy (IRT). IRT procedures typicallyutilize radioimagery systems, such as fluoroscopy, to position aradiation source within the injured length of the vessel, for example,the dilated portion of the vessel. The radioimagery system allows aradiation source, as well as radio-opaque markers, to be viewed in vivo.

For example, once a procedure, such as an angioplasty, is completed, thephysician may freeze-frame the radio-image on a viewer, such as afluoroscope, so that anatomical landmarks may be used to subsequentlyposition a radiation source within the dilated area. Typically, acatheter is inserted into the vessel and positioned within the dilatedportion of the vessel. Catheters used in IRT commonly have an elongate,tubular shaft for receiving a radiation source that will deliver theprescribed radiation therapy. Some catheters have markers, for example,radio-opaque markers, which denote the area of the catheter in which theradioactive source will be located. The markers may be viewed using theradioimagery system to assist in positioning the catheter within vessel.

Once the catheter is positioned, a radiation source is then advancedthrough the lumen of the catheter shaft, and positioned within thedilated portion of the vessel. Some IRT procedures utilize a radiationsource, such as radioactive seeds sealed within a source lumen, in whichthe source is visible on the radioimagery system, i.e., the fluoroscope.Other systems utilize radioactive sources that are not easily viewed,and, therefore, utilize markers, such as radio-opaque markers, that arevisible on the radioimagery system. These markers can be used to markone or both ends of the radiation source.

FIG. 1 illustrates a longitudinal cross-sectional view of one example ofa method in the prior art for inhibiting restenosis using IRT. Followingdilation of a vessel 10 using an angioplasty balloon length of 22 mm,the angioplasty balloon is removed and a catheter 12 is inserted andpositioned within the dilated length. In this example, the catheter 12may be a centering catheter designed to substantially center a radiationsource 16 within the vessel 10. The catheter 12 has radio-opaqueproximal and distal markers 14A and 14B that are designed to be visibleusing radioimagery. The markers 14A and 14B demarcate the area withinwhich the radiation source is located to allow positioning of thecatheter 12 within the vessel. The catheter 12 may be positioned usingstandard radioimagery techniques well known in the art in which, forexample, a fluoroscope is used to observe the incremental movement ofthe catheter 12 until the dilated length of the vessel 10 isapproximately centered between the proximal and distal markers 14A and14B. In this example, the proximal and distal markers 14A and 14Bdelineate a 27 mm region to provide a 5 mm margin of error inpositioning the dilated length (22 mm) within the radio-opaque markers14A and 14B. A 27 mm radioactive source 16, such as a radioactive sourcewire, is then inserted and positioned within the catheter 12 so that thesource end marker 18 is positioned over the distal radio-opaque marker14B on the catheter 12. In this way the radioactive source 16 is locatedbetween the markers 14A and 14B. The radioactive source 16 is left inplace until a prescribed radiation dose has been delivered to thevessel, and is then withdrawn.

A problem in current intravascular radiotherapy systems is theoccurrence of an edge effect, or severe narrowing, at one or more endsof the irradiated region. A possible cause of edge effects is deliveringa therapeutic dose of radiation that is too short in length to preventrestenosis throughout the treated vessel. Several factors may beresponsible for not treating an adequate length of the injured vessel.Some of these have been defined as positioning errors, underestimatingthe length of the injury which may be longer than the dilation lengthdue to the possibility of traumatizing segments of the vessel adjacentto the injury, and radiation dose fall-off.

Positioning of the radiation source relative to the freeze-framed imageis difficult due to some movement of the vessel resulting from patientmovement, blood flow, heart beats, and breathing. Thus, the radiationsource may not be correctly positioned within the injured portion of thevessel, resulting in a geographical miss.

A further contributor to geographical misses, results from the projectedangle of view by the radioimagery system. With radioimagery systems,such as fluoroscopy, the projected view is foreshortened so thatdistances appear shorter than a true perpendicular view would provide.Thus, positioning of a radiation source using a radio-image may resultin the source being incorrectly positioned relative to the vesselinjury.

In some cases, a minimum radiation source length may be chosen to treata vessel injury in an attempt to prevent overdosing of non-injuredlengths of vessel. If the radiation source was initially incorrectlypositioned as earlier described, the selection of a minimum radiationsource may result in some portions of the injured vessel left untreated.

Sometimes, during the intravascular procedures previous to the IRT,additional procedures are undertaken that cause more injury to a vesselthan was anticipated. For example, if a stent does not fully deploy, theballoon used to deploy the stent may be inflated to a higher pressure,or may be moved around in an attempt to fully deploy the stent. Thehigher inflation pressure and movement may cause damage to the vessel inareas adjacent to the main dilated or stented length. In anotherexample, a small blockage may be dilated outside a larger blockage in anattempt to touch-up the vessel and open it up. If this is done inseveral locations, often the radiation source is not positioned to treatthe touched up areas. In a third example, during a balloon dilation orstenting procedure, the balloon shoulders may stretch or tear the vesselin areas adjacent to the main dilated or stented area resulting in alonger portion of the vessel being injured. When a radiation source isinserted to deliver a prescribed dose of radiation to the procedurallyexpected injured portions of the vessel, these additionally damagedareas may not be known and may not receive a prescribed dose ofradiation.

Even if a radiation source is correctly positioned within the injuredportion of a vessel, a prescribed dose of radiation may not be deliveredalong the entire length of the source. Some radiation sources have adose fall-off region at the ends of the source where a lower dose ofradiation is delivered than in the middle of the source. These fall-offregions vary with the particular radiation source.

FIG. 2 illustrates an example of a longitudinal dose profile of aradiation source within a centering catheter in the prior art. In oneexample, a therapeutic dose of radiation may be defined as at least anisodose line at 80% of a prescribed dose at 1 mm in tissue, for example,80% of 20 Gy at 1 mm in tissue; and, a sub-therapeutic dose may bedefined as a dose below an isodose line at 80% of a prescribed dose at 1mm in tissue. It is to be understood that a therapeutic dose ofradiation may be differently defined depending upon the radiation sourceand treatment therapy.

The dose distribution illustrates that if a 27 mm radiation source 16 ispositioned correctly within the proximal and distal markers 14A and 14B,the 27 mm radiation source 16 delivers a full therapeutic dose ofradiation along a length of about 22 mm with a 2-2.5 mm dose fall off ateach end of the radiation source. Thus, the 27 mm radiation source 16delivers a full therapeutic dose of radiation along a length that isshorter than the total length of the radiation source. This leaveslittle to no margin for treating injured lengths beyond the dilatedlength and does not allow room for positioning errors arising from thetreatment system or physician.

Additionally, animal studies indicate that a ³²P radiation dose in therange of 5-11 Gy at 1 mm into the vessel can produce a negative,proliferative response in the vessel. This dose range may be termed aproliferative dose, and may result in restenosis, or renarrowing of thevessel, in the portions of the vessel that received the proliferativedose. As a result, vessels with maximum dilated lengths may haveportions of injured tissue adjacent to each side of the dilated lengthwhich may receive a less than therapeutic dose of radiation, and mayactually receive a proliferative dose of radiation, inducing edgeeffects.

As illustrated in the examples above, it is difficult to determine wherea therapeutic dose of radiation is being delivered to an injured lengthof vessel. Further, it is difficult to determine if additional damageexists in the vessel, and if that additional damage is receiving atherapeutic dose of radiation, or perhaps a proliferative dose ofradiation.

Thus, a need exists for a method and/or apparatus that delivers atherapeutic dose of radiation over an adequate length of a vessel toprevent restenosis following intravascular procedures such asangioplasty or stenting. Further, the method and/or apparatus shouldenable visualization of the length within which the therapeutic dose isdelivered.

SUMMARY OF THE INVENTION

The present invention includes methods and apparatuses for positioning aradiation source in vivo relative to radio-opaque markers on a catheterthat delineate a therapeutic treatment length so that a therapeutic doseof radiation is delivered along the therapeutic treatment length.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention may best be understood by referring to thefollowing description and accompanying drawings which are used toillustrate examples of the invention. In the drawings:

FIG. 1 illustrates a longitudinal cross-sectional view of one example ofa method in the prior art for inhibiting restenosis using IRT.

FIG. 2 illustrates an example of a longitudinal dose profile of aradiation source within a centering catheter in the prior art.

FIG. 3 illustrates a general overview of one embodiment of a methodaccording to the present invention for developing a total radiationsource length necessary to deliver a therapeutic dose of radiation overa therapeutic treatment length.

FIG. 4 illustrates a longitudinal cross-sectional view of one embodimentof a 2-marker catheter according to the present invention.

FIG. 5 illustrates a longitudinal cross-sectional view of one embodimentof a 3-marker catheter according to the present invention.

FIG. 6 illustrates a longitudinal cross-sectional view of one embodimentof a 2-marker catheter having an elongated marker according to thepresent invention.

FIG. 7 illustrates a longitudinal cross-sectional view of one embodimentof a 2-marker catheter with a dead end lumen according to the presentinvention.

FIG. 8 illustrates an external side view of one embodiment of aradiation source having a marker according to the present invention.

FIG. 9 illustrates an external side view of one embodiment of a 2-markerradiation source according to the present invention.

FIG. 10 illustrates a longitudinal cross-sectional view of oneembodiment of a radiation delivery system which includes a 2-markercatheter used in conjunction with a radiation source according to thepresent invention.

FIG. 11 illustrates a longitudinal cross-sectional view of oneembodiment of a radiation delivery system which includes a 2-markercatheter with dead end lumen used in conjunction with a radiation sourceaccording to the present invention.

FIG. 12 illustrates a longitudinal cross-sectional view of oneembodiment of a radiation delivery system which includes a 2-markercatheter used in conjunction with a radiation source having a markeraccording to the present invention.

FIG. 13 illustrates a longitudinal cross-sectional view of oneembodiment of a radiation delivery system which includes a 2-markercatheter having an elongated marker used in conjunction with a radiationsource according to the present invention.

FIG. 14 illustrates a longitudinal cross-sectional view of oneembodiment of a radiation delivery system which includes a 3-markercatheter used in conjunction with a radiation source according to thepresent invention.

FIG. 15A illustrates a longitudinal cross sectional view of oneembodiment of an inactive dummy source wire positioned within a 2-markercatheter according to the present invention.

FIG. 15B illustrates a longitudinal cross sectional view of oneembodiment of radioactive source wire positioned relative to thepositioning of the dummy source wire within the 2-marker catheter ofFIG. 15A according to the present invention.

FIG. 16 illustrates one embodiment of a radiation delivery device forpositioning a radiation source wire relative to a dummy source wireaccording to the present invention.

FIG. 17 illustrates a longitudinal cross-sectional view of a steppedcentering catheter having a stepped centering balloon that may be usedwith the present invention.

FIG. 18 illustrates a transverse cross-sectional view of the steppedcentering catheter of FIG. 17 taken at A—A.

FIG. 19 illustrates a transverse cross-sectional view of the steppedcentering catheter of FIG. 17 taken at B—B.

FIG. 20 illustrates an external side view of the stepped centeringcatheter of FIG. 17.

FIG. 21 illustrates a longitudinal cross-sectional view of anotherembodiment of a stepped centering catheter having a stepped centeringfluted balloon that may be used with the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention includes methods and devices for positioning aradiation source in vivo relative to radio-opaque markers on a catheterthat delineate a therapeutic length, so that a therapeutic dose ofradiation is delivered between the radio-opaque markers. By deliveringthe therapeutic dose along the therapeutic length, the present inventionmay help to prevent or eliminate restenosis following intravascularprocedures that injure a vessel.

To effectively reduce or inhibit restenosis, it is important to delivera therapeutic dose of radiation along an adequate length of the injuredvessel. A therapeutic dose of radiation may be defined as at least theminimum amount of radiation that will effectively reduce restenosis whendelivered to a prescribed location of a vessel. While it is difficult todetermine the “adequate length of the injured vessel” that shouldreceive the therapeutic dose of radiation, one embodiment of the presentinvention includes a method for approximating this length, called thetherapeutic treatment length, and determines a total radiation sourcelength required to deliver a therapeutic dose of radiation along thetherapeutic treatment length.

FIG. 3 illustrates a general overview of one example of one embodimentof a method for determining the total radiation source length neededdeliver a therapeutic dose of radiation over a therapeutic treatmentlength according to the present invention. According to one embodimentof the present invention, a total radiation source length necessary todeliver a therapeutic dose of radiation over a therapeutic treatmentlength may be calculated as:

TOTAL RADIATION SOURCE LENGTH=DILATED LENGTH OF VESSEL+IN VIVO FACTORSLENGTH+DOSE FALL OFF LENGTH+POSITIONING TOLERANCES OF RADIATION DELIVERYSYSTEM LENGTH (IF APPLICABLE)

Although the following examples are described in regard to a vesselinjured by a balloon dilation procedure, it is to be understood that thepresent invention may be used in treating vessels injured by proceduresother than angioplasty, or balloon dilation, and that the origin of theinjury to the vessel is not meant to be limiting on the presentinvention. For example, while the examples herein are discussed withregard to angioplasty, or dilatation procedures, the injury may arisefrom stenting, atherectomy, or other intravascular procedures.

In one example, a vessel may be dilated using a 23 mm angioplastyballoon resulting in an estimated maximum dilation length of 23 mm. Asearlier discussed, merely positioning a radiation source over theestimated dilation length may not provide a therapeutic dose ofradiation to an adequate length of vessel thus restenosis may not beprevented. Several in vivo factors may result in the radiation sourcebeing displaced from the injured length of vessel so that a longerlength of vessel, i.e., longer than the 23 mm dilated length, may needto be treated with a therapeutic dose of radiation. Examples, of in vivofactors that may be considered are additional injured lengths of vesseloutside the estimated dilated length, in vivo positioning errors, etc.

In dilating the vessel, there may be additional injured lengths ofvessel adjacent to the dilated length due to stretching or tearing ofthe intima from the dilation balloon, or other device. As earlierdiscussed, this additional injury is difficult to determine, and thusmay be estimated using experimental data, physician experience, or othersources of information.

Following the dilation, during delivery of the prescribed dose ofradiation using IRT, the radiation source may be displaced relative tothe injured length. These in vivo positioning errors may be due toinitial catheter placement relative to the injured length, andtranslation of the catheter/radiation source with respect to the injuredlength due to movement.

As earlier discussed, error in initial catheter placement may arise fromhaving to position the catheter in vivo by viewing the procedure usingradioimagery. Translation of the catheter/radiation source with respectto the injured length may arise from movement of the beating heart,blood flow in the vessel as the heart moves, as well as some patient andvessel movement as the heart beats. These in vivo positioning errors arealso difficult to determine and may be may be estimated usingexperimental data, physician experience, or other sources ofinformation. In one example, the above in vivo factors may be estimatedto total 11 mm.

Further, other factors related to the radiation source and the radiationdelivery method should be considered in developing a requisite totalradiation source length. These other factors may include the dose falloff of the particular radiation source, as well as source positioningand manufacturing tolerances associated with the radiation deliverydevice, if applicable.

As earlier discussed, radiation sources, and in particular, radioactiveline sources, have dose fall off regions where a drop in radiationintensity occurs at the ends of the source. The rate at which theradiation intensity falls, and consequently, the length of the sourcethat delivers a therapeutic dose to the prescribed location varies withdifferent isotopes and source configurations. Portions of the radiationsource which fall below the therapeutic dose level, may be termed thesub-therapeutic portions of the radiation source. Dose fall-offinformation may be obtained from radiochromic film analysis, and varieswith the particular radiation source.

For example, a ³²P radiation source may have dose fall off regionsapproximately 2 mm from each end, i.e., proximal and distal regions,where the dose is sub-therapeutic, i.e., a total of 4 mm. It is to beunderstood that this length is merely exemplary and that differentradiation sources may have different fall-off regions depending upon theparticular isotope and source configuration.

Further, radiation delivery devices, similar to most devices, have somesource positioning and manufacturing tolerances particular to thefabrication and operation of the device, and the radiation sourceutilized by the device.

For example, the radiation delivery device may be an automatedafterloader device which is described later with reference to FIG. 16.In one example, the afterloader device may utilize an inactive (ordummy) positioning source wire to determine the initial placement of anradioactive source wire relative to the catheter and then position theradioactive source wire relative to the inactive positioning wire. Thisinactive/radioactive positioning may result in some source positioningtolerances. Further, the radiation source positioned using theafterloader device may have source manufacturing tolerances, such asradiation source internal component shift error relating to tolerancesin the fabrication of the radioactive source wire and internalcomponents of the radioactive source wire. The source positioning andmanufacturing tolerances of the afterloader device may be estimatedusing standard tolerance and error measurement and analysis techniqueswell known to those of ordinary skill in the art. In one example thesource positioning and manufacturing tolerances may total 2.0 mm.

Using the above described values, a total radiation source length maythen be determined by adding the initial dilated length (for example, 23mm), a length to account for the in vivo factors (for example, 11 mm),the dose fall off length (for example, 4 mm), and, if applicable, thesource positioning and manufacturing tolerances of the radiationdelivery device (for example, 2 mm). Thus, the total radiation sourcelength may be, for example, 40 mm.

Following determination of the total radiation source length, the dosefall off length is subtracted from the total radiation source length todetermine the therapeutic length of source. For example, the 40 mm totalradiation source length minus a total 4 mm dose fall off length resultsin a 36 mm therapeutic length of source with 2 mm of sub-therapeuticlength at each of the proximal and distal ends of the radiation sourcelength. If, for example, the reference point in the illustration denotesthe distal end of a region within which a therapeutic dose of radiationis to be delivered, if no other sources of error or tolerances areconsidered, the total radiation source length would be advanced adistance 2 mm distal to the mark so that a therapeutic dose of radiationis delivered proximal to the mark.

However, if a radiation delivery system having source positioning andmanufacturing tolerances is utilized, the source positioning andmanufacturing tolerances may result in the location of the therapeuticlength of source being displaced within a range around the referencepoint. For example, using the earlier discussed source positioning andmanufacturing tolerances may result in the 36 mm therapeutic sourcelength being displaced relative to the reference point +/−2 mm.

Therefore a tolerance stacking of extremes may be performed on thesource positioning and manufacturing tolerances (including the dose falloff) to determine worst case positioning skews relative to the referencepoint. For example, using the earlier described values, a positioningskew of 6 mm distal to the reference point may be obtained. Continuingwith the above example, as the distal 2 mm of the total radiation sourcelength is sub-therapeutic due to the 2 mm dose fall off, 4 mm of theskewed length of total radiation source length contains a portion of the36 mm therapeutic length of source. Thus, in this example, 4 mm may besubtracted from the 36 mm therapeutic length of source to obtain a 32 mmtherapeutic treatment length. In positioning the total radiation sourcelength relative to the reference point, the distal end of the totalradiation source may be positioned a distance 4 mm distal to thereference point so that therapeutic dose of radiation is deliveredproximal of the reference point. In this way the distal end of theradiation source is extended past the reference point a distance whichincludes positioning tolerances.

Thus, according to one embodiment of a method of the present invention,the total radiation source length may be approximated as the minimumradiation source length that may be used to deliver a therapeutic doseof radiation along the therapeutic treatment length.

It is to be noted that in one embodiment, the positioning tolerances maybe determined by stacking the extreme tolerances, however, other methodsof error and tolerance analysis may also be used to arrive at a totalradiation source length which delivers a therapeutic dose of radiationto the therapeutic treatment length in accordance with the teachings ofthe present invention. Additionally, it is to be understood that othersources of error and tolerances may also be incorporated into the designof the total radiation source length.

Further, while one exemplary total radiation source length is described,it is to be understood that various total radiation source lengths maybe obtained for use with various dilation length indications. Thisapplies to solid line sources, as well as seed sources, which may bearranged in a line configuration by using multiple seeds, pellets withribbon sources, and source wires.

Also, smaller length radiation sources with multi-functional capabilitymay be used to achieve an effective total radiation source lengththrough the use of stepping protocols. Radiation sources, for example,radiation source wires, are expensive to produce, and have a timelimited efficacy due to radioactive decay. Thus, radiation sources areusually manufactured in only a few industry standard lengths. Forexample, there are currently over twelve different stent plus balloondilation lengths ranging from 16 mm to 44 mm. Requiring a differentsingle radiation source length to accommodate each of the specificlengths, could entail substantial expense for use in treating only afraction of the patients. Thus, in this and the following embodiments,although a single total radiation source length is discussed andillustrated, it is to be understood that a single radiation source,smaller than the total radiation source length, may be used according toa stepping protocol so that a therapeutic dose of radiation is deliveredalong the therapeutic treatment length. This allows the single, smallerradiation source to be used in treating therapeutic treatment length ofdiffering lengths.

The following figures illustrate several embodiments of methods andapparatuses according to the present invention that provide delivery ofa therapeutic dose of radiation along a therapeutic treatment lengthutilizing the method discussed in reference to FIG. 3. The followingfigures provide for visualization of the therapeutic treatment lengthalong which a therapeutic dose of radiation is delivered usingradio-opaque markers.

2-MARKER CATHETER

FIG. 4 illustrates a longitudinal cross-sectional view of one embodimentof a 2-marker catheter according to the present invention. As earlierdiscussed, positioning of a radiation source relative to an injury canbe difficult due to various sources of error and tolerances. To aid incorrect placement of the catheter relative to the injury, a method fordenoting the location of the therapeutic treatment length is beneficial.By clearly indicating the therapeutic treatment length, the potentialfor positioning errors and geographical misses is reduced as it iseasier to position the dilated portion of the vessel within thetherapeutic treatment length. Thus, according to one embodiment of thepresent invention, radio-opaque proximal and distal catheter markers arelocated on a catheter to define a therapeutic treatment length, ortherapeutic treatment length, in between, so that a radiation source maybe positioned relative to the markers to allow delivery of a therapeuticdose of radiation along the therapeutic treatment length.

In the embodiment illustrated in FIG. 4, the catheter 42 hasradio-opaque proximal and distal markers 44A and 44B located on thecatheter shaft 46. The shaft 46 is an elongate, tubular structure thathas a lumen for receiving a radiation source, not shown. The catheter 42may be either open or closed ended and may have other structures foraccepting a guidewire or support wire. The markers 44A and 44B arespaced apart so as to define a therapeutic treatment length, measured asthe distance between markers 44A and 44B. In one embodiment, thetherapeutic treatment length may be determined as earlier described withreference to FIG. 3. In one embodiment, the therapeutic treatment lengthmay be measured as the distance between the distal edge of the proximalmarker 44A and the proximal edge of the distal marker 44B. Thetherapeutic length denotes the region where the radiation source willdeliver a therapeutic dose of radiation when correctly positionedrelative to the markers 44A and 44B. Lengths of the vessel outside themarkers 44A and 44B may receive a sub-therapeutic dose. It is to benoted that the lumen of the shaft 42 is of a length that can receive thetotal radiation source length when correctly positioned so that atherapeutic dose of radiation is delivered along the therapeutictreatment length.

In one embodiment, the catheter 42 may be a centering catheter, such asa stepped centering catheter which substantially radially centers theportion of the radioactive source located within therapeutic treatmentlength within the vessel lumen and offsets portions of the radioactivesource located outside the therapeutic treatment length a minimumdistance from the vessel wall. An example of a stepped centeringcatheter is further described herein with reference to FIGS. 17-21. Inthis embodiment, the catheter markers 44A and 44B delineate thetherapeutic treatment length, as well as the length within which thetherapeutic treatment length is radially centered. Centering thetherapeutic portion of the radioactive source inside the vessel ensuresthat an approximately uniform therapeutic dose is delivered radially aswell as axially to the vessel. Offsetting the sub-therapeutic portionsof the radioactive source mitigates overdosing of the vessel wall. It isto be understood that other centering catheters, as well as othernon-centering catheters, may also be used.

In one embodiment, the catheter 42 may be positioned in a vessel lumenusing radioimagery so that the dilated length of vessel is substantiallylongitudinally centered between the proximal and distal catheter markers44A and 44B. It is to be understood that while the markers and imagingsystems are described in this and the following figures with referenceto radioimagery, such as fluoroscopy, and markers, such as radio-opaquemarkers, that can be viewed using radioimagery, other markers andimaging systems may also be used. It is to be understood that the lengthof the catheter 42 and the therapeutic treatment length denoted by theproximal and distal catheter markers 44A and 44B are chosen based uponthe initial dilated length of the treated site and such other factors asthose earlier discussed in regard to FIG. 3.

In one example, the catheter 42 may coupled to a radiation deliverydevice, such as an afterloader device, with a key connector thatprovides the afterloader device with information regarding theparticular catheter, i.e., diameter, length, therapeutic length, andmarker locations. This information may allow the afterloader device todetermine the positioning of a radiation source relative to the cathetermarkers 44A and 44B, so that a therapeutic dose is delivered along thetherapeutic treatment length. It is to be understood that the catheter42 is not required to be used with an automated afterloader device orkey connector, and that a manual radiation delivery device or otherautomated (including semi-automated) radiation delivery device may beused.

Once the therapeutic treatment length delineated by the markers 44A and44B has been positioned within the vessel, the markers 44A and 44B maybe used for positioning a radiation source inside the catheter so that atherapeutic dose of radiation is delivered along the therapeutictreatment length. In this way, the present invention visually demarcatesthe length along which a therapeutic dose of radiation is delivered to avessel. This is contrast to prior art methods of delivering IRT whichdid not clearly demarcate the area in which a therapeutic dose ofradiation is delivered. Positioning a radiation source relative to themarkers 44A and 44B so that a therapeutic dose of radiation is deliveredalong the therapeutic treatment length may be accomplished by severalmeans as described in the several embodiments of the present inventionthat follow.

3-MARKER CATHETER

FIG. 5 illustrates a longitudinal cross-sectional view of one embodimentof a 3-marker catheter according to the present invention. In theembodiment illustrated in FIG. 5, the catheter 52 has a radio-opaqueproximal and distal markers 44A and 44B that delineate a therapeutictreatment length and an additional third marker, a source positioningmarker 56. In one embodiment, the catheter 52 maybe a centeringcatheter, such as a stepped centering catheter which substantiallyradially centers the portion of the radioactive source located withintherapeutic treatment length within the vessel lumen and offsetsportions of the radioactive source located outside the therapeutictreatment length a minimum distance from the vessel wall. An example ofa stepped centering catheter is further described herein with referenceto FIGS. 17-21. The source positioning marker 56 is located a distancedistal to marker 44B and is used in positioning a radiation sourcerelative to markers 44A and 44B so that a therapeutic dose of radiationis delivered along the therapeutic treatment length. In one embodiment,the distance is equal to at least the distal length of thesub-therapeutic portion of the radiation source to be inserted, and mayfurther include a length for positioning tolerances as earlier describedin reference to FIG. 3. In this way depending upon the radiation sourceand radiation source delivery device, the distal end of the radiationsource may be advanced to the source positioning marker 56 to allow atherapeutic dose of radiation to be delivered along the therapeutictreatment length.

Alternatively, the source positioning marker 52 may be located instead adistance proximal to the proximal marker 44A. In one embodiment, thedistance is equal to at least the proximal length of the sub-therapeuticportion of the radiation source to be inserted, and may further includea length for positioning tolerances as earlier described in reference toFIG. 3. In this alternative embodiment, the proximal end of theradiation source would be advanced to the source positioning marker 56to allow a therapeutic dose of radiation to be delivered along thetherapeutic treatment length.

2-MARKER CATHETER, ELONGATED MARKER

FIG. 6 illustrates a longitudinal cross-sectional view of one embodimentof a 2-marker catheter having an elongated marker according to thepresent invention. In the embodiment illustrated in FIG. 6, the catheter62 has a radio-opaque proximal and distal markers 64A and 64B thatdelineate a therapeutic treatment length as earlier described inreference to FIG. 3 and FIG. 4. In one embodiment, the catheter 62 maybe a centering catheter such as a stepped centering catheter whichsubstantially radially centers the portion of the radioactive sourcelocated within therapeutic treatment length within the vessel lumen andoffsets portions of the radioactive source located outside thetherapeutic treatment length a minimum distance from the vessel wall. Anexample of a stepped centering catheter is further described herein withreference to FIGS. 17-21. In this embodiment, the marker 64B is distallyelongated a distance outside the therapeutic treatment length and isused in positioning a radiation source so that a therapeutic dose ofradiation is delivered along the therapeutic treatment length. In oneembodiment, the elongated distance is equal to at least the distallength of the sub-therapeutic portion of the radiation source to beinserted, and may further include a length for positioning tolerances asearlier described in reference to FIG. 3. In this way depending upon theradiation source and radiation source delivery device, the distal end ofthe radiation source may be advanced until it just exits the distal sideof the elongated marker 64B, so that a therapeutic dose of radiation isdelivered along the therapeutic treatment length.

Alternatively, the proximal marker 64A may be proximally elongated adistance outside the therapeutic treatment length. In one embodiment,the elongated distance is equal to at least the proximal length of thesub-therapeutic portion of the radiation source to be inserted, and mayfurther include a length for positioning tolerances as earlier describedin reference to FIG. 3. In this alternative embodiment, the proximal endof the radiation source may be advanced until the proximal end of theradiation source just passes inside the proximal edge of the elongatedproximal marker 64A, so that a therapeutic dose of radiation isdelivered along the therapeutic treatment length.

2-MARKER CATHETER WITH A DEAD END LUMEN

FIG. 7 illustrates a longitudinal cross-sectional view of one embodimentof a 2-marker catheter with a dead end lumen according to the presentinvention. In the embodiment illustrated in FIG. 7, the catheter 72 hasa radio-opaque proximal and distal markers 74A and 74B that delineate atherapeutic treatment length and a dead end lumen 76. In one embodiment,the catheter 72 may be a centering catheter such as a stepped centeringcatheter which substantially radially centers the portion of theradioactive source located within therapeutic treatment length withinthe vessel lumen and offsets portions of the radioactive source locatedoutside the therapeutic treatment length a minimum distance from thevessel wall. An example of a stepped centering catheter is furtherdescribed herein with reference to FIGS. 17-21. The dead end lumen 76terminates at a distance distal to marker 74B and is used in positioninga radiation source relative to markers 74A and 74B so that a therapeuticdose of radiation is delivered along the therapeutic treatment length.In one embodiment, the dead end lumen 76 is located a distance equal toat least the distal sub-therapeutic region of the radiation source to beinserted, and may further include a length defined by one or more of thepositioning earlier described in reference to FIG. 3. In this way,depending upon the radiation source and radiation source deliverydevice, the distal end of the radiation source may be advanced until itstops at the dead end lumen 76 so that a therapeutic dose of radiationto be delivered along the therapeutic treatment length.

1-MARKER RADIATION SOURCE

FIG. 8 illustrates an external side view of one embodiment of aradiation source having a marker according to the present invention. Inthe embodiment illustrated in FIG. 8, the radiation source 80 has aradio-opaque marker 82 that located within the radioactive region 84 ofsaid radiation source 80. The marker 82 may be used in positioning theradiation source 80 relative to markers 44A and 44B illustrated withreference to FIG. 4 so that a therapeutic dose of radiation is deliveredalong the therapeutic treatment length. In one embodiment, the radiationregion 84 may further have a therapeutic dose region 88 and proximal anddistal sub-therapeutic dose regions 86A and 86B located at each end ofthe therapeutic dose region 88. In one embodiment the marker 82 may belocated at a distance proximal to the distal end of the radiation source80 where the distance is at least the length of the distalsub-therapeutic dose region 86B. This distance may further include alength define by one or more positioning tolerances as discussed inreference to FIG. 3. In this way depending upon the radiation source andradiation source delivery device, the marker 82 may be aligned with amarker such as the marker 44B in FIG. 4, so that a therapeutic dose ofradiation may be delivered along the therapeutic treatment length.

Alternatively, the marker 82 may be located instead a distance distal tothe proximal end of the radiation source 80 where the distance is atleast equal to the length of the proximal sub-therapeutic dose region86A, and may further include a length define by one or more positioningtolerances as discussed in reference to FIG. 3. In this way dependingupon the radiation source and radiation source delivery device, themarker 82 may be aligned with a marker such as the marker 44A in FIG. 4,so that a therapeutic dose of radiation may be delivered along thetherapeutic treatment length.

2-MARKER RADIATION SOURCE

FIG. 9 illustrates an external side view of one embodiment of a 2-markerradiation source according to the present invention. In the embodimentillustrated in FIG. 9, the radiation source 90 has proximal and distalradio-opaque markers 92A and 92B that are located within the radioactiveregion 94 of said radiation source 90. The markers 92A and 92B may beused in positioning the radiation source 90 within a catheter so that atherapeutic dose of radiation is delivered between the markers 92A and92B. In one embodiment, the radiation source 90 may be used inconjunction with a centering catheter such as a stepped centeringcatheter which substantially radially centers the portion of theradioactive source located within therapeutic treatment length withinthe vessel lumen and offsets portions of the radioactive source locatedoutside the therapeutic treatment length a minimum distance from thevessel wall. An example of a stepped centering catheter is furtherdescribed herein with reference to FIGS. 17-21. In one embodiment, theradiation region 94 may further have a therapeutic dose region 98 andproximal and distal sub-therapeutic dose regions 96A and 96B located ateach end of the therapeutic dose region 98. In one embodiment, themarkers 92A and 92B may be spaced apart so as to define the therapeuticdose region 98 of the radiation source 90.

RADIATION DELIVERY SYSTEM INCLUDING A 2-MARKER CATHETER AND ARADIOACTIVE SOURCE

FIG. 10 illustrates a longitudinal cross-sectional view of oneembodiment of a radiation delivery system which includes a 2-markercatheter used in conjunction with a radiation source according to thepresent invention. In one embodiment, the catheter 100 is used inconjunction with a radiation source 104 so that a therapeutic dose ofradiation is delivered between the proximal and distal radio-opaquemarkers 102A and 102B. In one embodiment, the catheter 100 may be acentering catheter such as a stepped centering catheter whichsubstantially radially centers the portion of the radioactive sourcelocated within therapeutic treatment length within the vessel lumen andoffsets portions of the radioactive source located outside thetherapeutic treatment length a minimum distance from the vessel wall. Anexample of a stepped centering catheter is further described herein withreference to FIGS. 17-21.

In one embodiment, the radiation source 104 may have radioactive region106 which includes a therapeutic dose region 108 and proximal and distalsub-therapeutic dose regions 110A and 110B. In one embodiment, themarkers 102A and 102B may be spaced apart along the catheter 100 at adistance less than or equal to the therapeutic dose region 108 of theradiation source 106. In another embodiment, the markers 102A and 102Bmay be spaced apart along the catheter 100 at a distance less than orequal to the therapeutic dose region 108 minus a distance forpositioning tolerances as earlier discussed in reference to FIG. 3. Toaccommodate the sub-therapeutic dose regions 110A and 110B, the lumen ofthe catheter 100 extends a distance proximal and distal to the markers102A and 102B, each distance being at least equal to the respectivesub-therapeutic dose regions 110A and 110B, and may include anadditional length for positioning tolerances as discussed with referenceto FIG. 3. In this way, a therapeutic dose of radiation is deliveredbetween the markers 102A and 102B.

RADIATION DELIVERY SYSTEM INCLUDING A 2-MARKER CATHETER WITH DEAD ENDLUMEN AND A RADIOACTIVE SOURCE

FIG. 11 illustrates a longitudinal cross-sectional view of oneembodiment of a radiation delivery system which includes a 2-markercatheter with dead end lumen used in conjunction with a radiation sourceaccording to the present invention. In this embodiment, the catheter 120is used in conjunction with a radiation source 122 so that a therapeuticdose of radiation is delivered between the first and second radio-opaquemarkers 124A and 124B. In one embodiment, the catheter 120 may be acentering catheter such as a stepped centering catheter whichsubstantially radially centers the portion of the radioactive sourcelocated within therapeutic treatment length within the vessel lumen andoffsets portions of the radioactive source located outside thetherapeutic treatment length a minimum distance from the vessel wall. Anexample of a stepped centering catheter is further described herein withreference to FIGS. 17-21.

In one embodiment, the radiation source 122 may have a radioactiveregion 126 which includes proximal and distal sub-therapeutic doseregions 128A and 128B and a therapeutic dose region 130 located inbetween. Marker 124B may be located a distance proximal to the dead endlumen 132. In one embodiment, this distance is equal to at least thelength of the distal sub-therapeutic dose region 128B of the radiationsource 122, and may also further include a positioning tolerance lengthas discussed in reference to FIG. 3. Marker 124A is located a distanceproximal to marker 124B equal to the therapeutic dose region 130 of theradiation source 122.

RADIATION DELIVERY SYSTEM INCLUDING A 2-MARKER CATHETER AND A RADIATIONSOURCE HAVING A MARKER

FIG. 12 illustrates a longitudinal cross-sectional view of oneembodiment of a radiation delivery system which includes a 2-markercatheter used in conjunction with a radiation source having a markeraccording to the present invention. In this embodiment, the catheter 140is used in conjunction with a radiation source 142 having a first marker146 so that a therapeutic dose of radiation is delivered between thesecond and third radio-opaque markers 144A and 144B. In one embodiment,the catheter 140 may be a centering catheter such as a stepped centeringcatheter which substantially radially centers the portion of theradioactive source located within therapeutic treatment length withinthe vessel lumen and offsets portions of the radioactive source locatedoutside the therapeutic treatment length a minimum distance from thevessel wall. An example of a stepped centering catheter is furtherdescribed herein with reference to FIGS. 17-21.

In one embodiment, the radiation source 142 may have radioactive region148 which includes a therapeutic dose region 150 and proximal and distalsub-therapeutic dose regions 152A and 152B. In one embodiment, the firstmarker 146 is located a distance proximal to the distal end theradiation source 142 that is equal to at least the length of the distalsub-therapeutic dose region 152B. The distance may also further includea positioning tolerance length as discussed in reference to FIG. 3.Markers 144A and 144B are spaced apart along the catheter 140 at adistance less than or equal to the therapeutic dose region 150 of theradiation source 142. In this way the marker 146 is advanced within thecatheter 140 until the marker 146 is substantially aligned with thedistal marker 144B so that a therapeutic dose of radiation is deliveredbetween the markers 144A and 144B.

In another embodiment, the radiation source 142 may have the marker 146located a distance distal to the proximal end of the radiation source142. In one embodiment, the distance may be equal to at least the lengthof the proximal sub-therapeutic dose region 152A. The distance may alsofurther include a positioning tolerance length. In this way the marker146 is advanced within the catheter 140 until the marker 146 issubstantially aligned with the proximal marker 144A so that atherapeutic dose of radiation is delivered between the markers 144A and144B.

RADIATION DELIVERY SYSTEM INCLUDING A 2-MARKER CATHETER HAVING ANELONGATED MARKER AND A RADIATION SOURCE

FIG. 13 illustrates a longitudinal cross-sectional view of oneembodiment of a radiation delivery system which includes a 2-markercatheter having an elongated marker used in conjunction with a radiationsource according to the present invention. In this embodiment, thecatheter 160 is used in conjunction with a radiation source 162 so thata therapeutic dose of radiation is delivered between the proximal anddistal radio-opaque markers 164A and 164B. In one embodiment, thecatheter 160 may be a centering catheter such as a stepped centeringcatheter which substantially radially centers the portion of theradioactive source located within therapeutic treatment length withinthe vessel lumen and offsets portions of the radioactive source locatedoutside the therapeutic treatment length a minimum distance from thevessel wall. An example of a stepped centering catheter is furtherdescribed herein with reference to FIGS. 17-21.

In one embodiment, the radiation source 162 may have radioactive region166 which includes a therapeutic dose region 168 and proximal and distalsub-therapeutic dose regions 170A and 170B. In one embodiment, theproximal and distal markers 164A and 164B are spaced a distance apart soas to define a therapeutic treatment length. In one embodiment, thedistal marker 164B is distally elongated outside the therapeutictreatment length a distance equal to at least the length of the distalsub-therapeutic dose region 170B. The distance may also further includea length for positioning tolerances as discussed in reference to FIG. 3.The radiation source 162 may be positioned within the catheter 160 sothat the distal end of the radioactive region 166 just exits the distalend of the distal elongated marker 164B. In this way a therapeutic doseof radiation is delivered along the therapeutic treatment length betweenmarkers 164A and 164B.

In another embodiment, the proximal marker 164A is proximally elongatedoutside the therapeutic treatment length a distance equal to at leastthe length of the proximal sub-therapeutic dose region 170A. Thedistance may also further include a length for positioning tolerances.The radiation source 162 may be positioned within the catheter 160 sothat the proximal end of the radioactive region 166 just enters theproximal end of the elongated proximal marker 164A. In this way atherapeutic dose of radiation is delivered along the therapeutictreatment length.

RADIATION DELIVERY SYSTEM INCLUDING A 3-MARKER CATHETER AND A RADIATIONSOURCE

FIG. 14 illustrates a longitudinal cross-sectional view of oneembodiment of a radiation delivery system which includes a 3-markercatheter used in conjunction with a radiation source according to thepresent invention. In this embodiment, the catheter 200 is used inconjunction with a radiation source 202 so that a therapeutic dose ofradiation is delivered along a therapeutic treatment length 208. In oneembodiment, catheter 200 includes first and second radio-opaque markers204A and 204B which are spaced a distance apart so as to define atherapeutic treatment length and a third radio-opaque marker 204Clocated outside the therapeutic treatment length 208. In one embodiment,the catheter 200 may be a centering catheter such as a stepped centeringcatheter which substantially radially centers the portion of theradioactive source located within therapeutic treatment length withinthe vessel lumen and offsets portions of the radioactive source locatedoutside the therapeutic treatment length a minimum distance from thevessel wall. An example of a stepped centering catheter is furtherdescribed herein with reference to FIGS. 17-21.

In one embodiment, the radiation source 202 may have radioactive region206 which includes a therapeutic dose region 208 and proximal and distalsub-therapeutic dose regions 210A and 210B. In one embodiment, the thirdmarker 204C is located a distance distal to the distal marker 204B. Inone embodiment, the distance may be equal to the length of the distalsub-therapeutic dose region 210B, and may further include a length forpositioning tolerances as discussed in reference to FIG. 3. In this way,the radiation source 202 is positioned within the catheter 200 so thatthe distal end of the radioactive region 206 just exits the marker 204Cso that a therapeutic dose of radiation is delivered along thetherapeutic treatment length 208.

RADIATION DELIVERY SYSTEM INCLUDING A 2-MARKER CATHETER AND RADIOACTIVESOURCE POSITIONED RELATIVE TO A DUMMY SOURCE

FIGS. 15A and 15B illustrate a longitudinal cross sectional view ofanother embodiment of a radiation delivery system according to thepresent invention including a 2-marker catheter and a radioactive sourcewire which is positioned relative to the positioning of a dummy sourcewire. An inactive dummy source wire is first positioned within thecatheter relative to the distal marker, and then an active source wireis positioned relative to the positioning of the dummy source wire.

FIG. 15A illustrates a longitudinal cross sectional view of oneembodiment of an inactive dummy source wire positioned within a 2 markercatheter according to the present invention. In one embodiment, thecatheter 230 includes radio-opaque proximal and distal catheter markers232A and 232B that are spaced apart to define a therapeutic treatmentlength 238. In one embodiment, the catheter 230 may be a centeringcatheter such as a stepped centering catheter which substantiallyradially centers the portion of the radioactive source located withintherapeutic treatment length within the vessel lumen and offsetsportions of the radioactive source located outside the therapeutictreatment length a minimum distance from the vessel wall. An example ofa stepped centering catheter is further described herein with referenceto FIGS. 17-21. It is to be understood that the catheter 230 may also beanother type of centering catheter, or a non-centering catheter.

In one embodiment, an inactive dummy source wire 234 is initiallypositioned in the catheter 230. In one embodiment, the dummy source wire234 may be a polymide tube with an inactive end plug of 1 mm NiTi. Thedummy source wire 234 may further have a distal radio-opaque marker 236,such as a tungsten band, which may be twice as long as the radio-opaquecatheter markers 232A and 232B. The catheter 230 may be connected to aradiation delivery device, such as an automated afterloader devicediscussed herein with reference to FIG. 16, that advances the dummysource wire 234 within the catheter 230. It is to be understood that thedummy source wire 234 may be also be positioned by devices other than anafterloader or manually.

The dummy source wire 234 is advanced within the catheter 230 until themarker 236 is correctly positioned relative to the distal marker 232B.In one embodiment, the marker 236 may be correctly positioned when it issubstantially aligned with the distal marker 232B. The length the dummysource wire 234 is advanced to the correct positioning relative tomarker 232B may be termed a first location and is recorded. The firstlocation may be recorded by the afterloader device, manually, or byother means. The dummy source wire 234 is then retracted and aradioactive source wire is then advanced into the catheter 230.

FIG. 15B illustrates a longitudinal cross sectional view of oneembodiment of radioactive source wire positioned relative to thepositioning of the dummy source wire within the 2 marker catheter ofFIG. 15A according to the present invention. After the dummy source wire234 is retracted, a radioactive source wire 240 is advanced to a secondlocation relative to the first location. In one embodiment, theradioactive source wire 240 may include proximal and distalsub-therapeutic dose regions 244A and 244B and a therapeutic dose region246 in between. In one embodiment, the radioactive source wire 240 mayhave the same specifications as the dummy source wire 240, but with theradioactive source material added. Thus, in one embodiment, theradioactive source wire 240 may be a polymide tube with a radiationsource of ³²P and a radio-opaque distal source end marker 242. It is tobe understood that isotopes other than ³²P may be used in the presentinvention. Further, a marker 242 is not necessary if the radiationsource is visible using the radioimagery system used during theprocedure, and the end of the radiation source can be seen.

In one embodiment, the afterloader may advance the radioactive sourcewire 240 within the catheter 230 so that it overshoots the firstlocation and is then distally retracted to a second location. In oneembodiment, the second location may be located a distance distal to thefirst location equal to at least the distal sub-therapeutic dose region244B, and may further include a positioning tolerance length. Thisintentional distal positioning allows the initial distal portion of thetherapeutic treatment length to receive a therapeutic dose. In this waya therapeutic dose of radiation is delivered along the therapeutictreatment length.

In another embodiment, a dummy source wire 234 is not required. In thisother embodiment, the radioactive source wire 240 is advanced to thedistal marker 232B, i.e., to the first location. Once the first locationis recorded, the radioactive source wire 240 is then advanced anadditional pre-determined length distal to the first location, i.e., tothe second location. In one embodiment, the additional pre-determinedlength may be equivalent to at least the length of the distalsub-therapeutic dose region 244B, and may further include a positioningtolerance length. Once the radioactive source wire 240 has been advancedthe pre-determined distance distal to the first location, it may be leftin place until a prescribed therapeutic dose of radiation has beendelivered along the therapeutic treatment length.

Although the radiation delivery systems described in FIGS. 10-15 havebeen illustrated using a single radiation source equal to the totalradiation source length, it is to be understood that, as earlierdiscussed, the radiation source used in the systems may be a smallerradiation source length used according to a stepping protocol whichcreates an effective total radiation source length, so that atherapeutic dose is delivered along the therapeutic treatment length.Additionally, although the inactive dummy radiation source is describedabove as a dummy source wire, other radiation sources may be used andthus, other inactive versions of those sources may also be used.

RADIATION DELIVERY DEVICE

FIG. 16 illustrates one embodiment of a radiation delivery device forpositioning a radiation source wire relative to a dummy source wireaccording to the present invention. As discussed with reference to FIGS.15A and 15B the catheter 230 may be connected to a radiation deliverydevice 300 via a connector 310 to allow advancement and retraction of aninactive radiation source, such as the inactive dummy wire 234, and ofan active radiation source, such as the radioactive source wire 240,within the catheter 230. The catheter 230 may have a connector key 320which attaches to connector 310. In one embodiment, the connector key320 may provide parameters pertaining to the catheter 230 to theafterloader device 300. In one embodiment the catheter 230 may be acatheter as discussed with reference to FIGS. 15A and 15B. In oneembodiment, the radiation delivery device 300 may be an afterloaderwhich includes an inactive radiation source which is positionable withinthe catheter 230 and a means for positioning the inactive radiationsource at a first location within the catheter 230. Additionally, theradiation delivery device 300 includes an active radiation sourcepositionable within the catheter 230 and a means for positioning anactive radiation source relative to the first location after theinactive radiation source is retracted from the catheter 230. Further,the radiation delivery device 300 includes a means for recording thefirst location.

The radiation delivery device 300 may also include a means for manuallyinputting data; a means for receiving manually input data; a means foroutputting data for display; and a means for displaying data. In oneembodiment these means may embodied as a computer system 330 having akeyboard, display, CPU with memory and input and output ports to allowcommunication between the radiation delivery device 300 and the computersystem 330.

STEPPED CENTERING CATHETER

As discussed with regard to the various embodiments of the presentinvention described above with reference to FIGS. 3-16, a radiationsource may be positioned within a catheter relative to radio-opaquemarkers so that a therapeutic dose of radiation is delivered along atherapeutic treatment length. The catheter may also substantially centera portion of the radioactive source within the vessel along thetherapeutic treatment length so that an approximately uniform dose ofradiation is delivered. However, in order to deliver the therapeuticdose within the therapeutic treatment length, portions of theradioactive source may extend beyond the centered therapeutic treatmentlength. Extending the radiation source beyond the centered therapeutictreatment length may result in overdosing the vessel wall if portions ofthe extended radiation source become positioned too close to a vesselwall. Thus, a stepped centering catheter having a stepped centeringballoon may be used to substantially center a portion of the radioactivesource within the vessel along the therapeutic treatment length and tomitigate overdosing of the vessel wall by offsetting the portions of theradiation source that extend outside the therapeutic treatment length aminimum distance from the vessel wall.

FIG. 17 illustrates a longitudinal cross-sectional view of oneembodiment of a stepped centering catheter having a stepped centeringballoon that may be used with the present invention. The steppedcentering balloon catheter 440 illustrated in FIG. 17 includes anelongate, tubular shaft 442 and a stepped centering balloon segment 444.The shaft 442 has a proximal end to allow introduction of a radioactivesource 450, such as a radioactive source wire, into the shaft lumen 448,and may have an open or closed distal tip 446. The radioactive source450 may have proximal and distal radio-opaque source markers 458 toenhance visualization by radioimagery systems, such as fluoroscopy. Theradio-opaque source markers 458 may be formed of tungsten, or of othermaterials, such as gold, or platinum.

The proximal end of the stepped centering balloon catheter 440 may beconnected to a radiation source delivery device such as an afterloader,or other device, for advancing a radiation source within the steppedcentering balloon catheter 440. For example, an afterloader produced byGuidant Corporation, Houston, Tex., may be used. If an afterloader isused in conjunction with the present invention, the stepped centeringballoon catheter 440 may be connected to the afterloader systemutilizing a key connector that allows the afterloader system to identifythe particular characteristics of the stepped centering catheter.

As illustrated in FIG. 17, the stepped centering balloon segment 444 maybe formed as a continuous, inflatable helical balloon that forms lobes454 around the shaft 442. An inflation lumen may be provided at theproximal end of the stepped centering balloon segment 444 to allowinflation from a pump or other inflation apparatus.

The stepped centering balloon segment 444 may include a central balloonsegment 460 of a first diameter and offset balloon segments 462 of asmaller, second diameter. It is to be noted that when inflated, thenature of a helical balloon is such that as the lobes 454 advance andspiral around the length of the shaft 442, an effective diameter iscreated which limits the radial positioning of the radiation source 450within the vessel 456.

The stepped centering balloon catheter 440 may have proximal and distalradio-opaque markers 452A and 452B attached to the shaft 442 thatdelineate the proximal and distal ends of the central balloon segment460. In this way, the markers 452A and 452B delineate the portion of theradiation source 450 that is substantially centered within the vessellumen.

In use, the stepped centering balloon catheter 440 is selected so thatwhen properly inflated, the first effective diameter of the centralballoon segment 460 is sized to be just large enough to compliantlyengage the walls of vessel 456 and to substantially center the shaftlumen 448, and, thus, a portion of the radiation source 450, within thelumen of the vessel 456. For example, the first effective diameter ofthe central balloon segment 460 may be determined to substantiallycenter a portion of the radiation source 450 which may deliver atherapeutic dose of 20 Gy at 1 mm into the vessel. The first effectivediameter of the central balloon segment 460 is stepped down to thesmaller, second effective diameter of the offset balloon segments 462across first steps 464. In this example, the first effective diameter ofthe central balloon segment 460 is continued to the interior edges ofthe markers 452A and 452B, i.e., the therapeutic treatment length. Thus,the central balloon segment 460 substantially centers the therapeuticdose region of radiation source 450 between the markers 452A and 452B.The first effective diameter is then gradually tapered to the secondeffective diameter along the length of the first steps 464.

The second effective diameter of the offset balloon segments 462 issized to offset portions of the radiation source 450 which extend beyondthe central balloon segment 460 within a region having a minimum offsetdistance from the vessel wall. In this way, the radiation dose deliveredto the vessel wall from the portions of the radiation source 450 thatextend beyond the central balloon segment 460 may be controlled toprevent overdosing the vessel. For example, the second effectivediameter of the offset balloon segments 462 may be determined to limitthe radiation dose delivered by the portions of the radiation source 450which extend beyond the central balloon segment 460, as discussed above,to 100 Gy or less at the vessel surface. Thus, the offset balloonsegments 462 offset sub-therapeutic portions of the radiation source 450that extend outside the markers 452A and 452B to prevent overdosing thevessel. Additionally, although the offset balloon segments 462 mayextend beyond the therapeutic treatment length of the vessel, thesmaller, second effective diameter should not cause or exacerbatestretches or tears in the vessel, thus mitigating further damage to thevessel.

It is to be noted that although the present embodiment is shown havingoffset balloon segments 462 both proximal and distal to the centralballoon segment 460, in alternative embodiments, the present inventionmay have only a proximal offset balloon segment 462 or a distal offsetballoon segment 462 with the corresponding first and second steps. Inthese embodiments, the opposite side of the central balloon segment 460without an offset balloon segment 462 may retain a first step 464tapering the first effective diameter to the diameter of the shaft 442.In other embodiments, the diameter of the shaft 442 may be sufficientlysimilar to the first effective diameter so that the opposite side of thecentral balloon segment 460 without an offset balloon segment 462 maynot require a first step 464.

The second effective diameter of the offset balloon segments 462 isstepped down to the smaller diameter of the shaft 442 across secondsteps 466. In this example, the second effective diameter of the offsetballoon segments 462 is continued to the end of the radiation source450. The second effective diameter is then gradually tapered to thediameter of the shaft 442 along the length of the second steps 466. Thefirst steps 464 and second steps 466 allow for a gradual increase andreduction in the effective diameters created by the helical lobes 454 asthe stepped centering balloon catheter 440 is positioned within thevessel. The gradual tapering is provided to allow the vessel walls togradually respond to the differences in diameters of the centeringballoon catheter 440 structure in an attempt to mitigate additionaldamage to the vessel.

The stepped centering balloon segment 444 may be fabricated usingstandard techniques well known to those of ordinary skill in the art. Inone embodiment, the stepped centering balloon segment 444 may befabricated using a shape mold and materials of relatively high strengththat will expand to a fixed diameter when inflated, such as relativelyhigh strength polymers, i.e., nylon, polyester, or polyvinyl acetate orpolyethylene. The stepped centering balloon segment 444 is attached tothe shaft 442 by bonds that are located at the ends of the steppedcentering balloon segment 444. The bonds may be thermal or ultrasonicwelds, adhesive or solvent bonds, or may be formed by other conventionalmeans well known to those of ordinary skill in the art.

The radio-opaque markers 452A and 452B may be gold, platinum, or othermaterials commonly viewable using radioimagery systems, such asfluoroscopy. The radio-opaque markers 452A and 452B may be attached tothe shaft 442 by conventional means well known to those of ordinaryskill in the art. In one embodiment, the radio-opaque markers 452A and452B may be attached to the shaft 442 immediately outside the centralballoon segment 460 to delineate the endpoints of the central balloonsegment 460. It will be appreciated that when used with the presentinvention, the length of the central balloon segment 460 may bedetermined according to the therapeutic treatment length calculated fora particular vessel. In this way, using radioimagery systems, theradio-opaque markers 452A and 452B provide a visual landmark of theportion of the radioactive source 450 that is substantially centeredwithin the vessel.

FIG. 18 illustrates a transverse cross-sectional view of the steppedcentering catheter of FIG. 17 taken at A—A. In the illustration, theradiation source 450 within the shaft 442 is substantially centeredwithin the lumen of the vessel 456 due to the first effective diameter470 created by the helical lobes 454 of the central balloon segment 460.This allows for an approximately uniform dose of radiation to bedelivered to the vessel wall along the therapeutic treatment length. Inthe illustration, a support mandrel lumen 472 is shown attached to theshaft 442 to allow insertion of a support mandrel 474. The supportmandrel 474 may be introduced proximal to the stepped centering balloonsegment 444 and may run substantially the length of stepped centeringsegment 444 and terminate at the distal tip 446. The support mandrellumen 472 and support mandrel 474 may be formed and attached to theshaft 442 using methods well known to those of ordinary skill in theart. It is to be understood that other embodiments without a supportmandrel lumen 472 and support mandrel 474 may also be used. Further itis to be understood that the present invention may also be formed with aguidewire lumen for accepting a guidewire, but that the use of aguidewire is not necessary, and is not meant to limit the scope of thepresent invention.

FIG. 19 illustrates a transverse cross-sectional view of the steppedcentering catheter of FIG. 17 taken at B—B. In this embodiment, theradiation source 450 is located within the shaft 442 and is maintainedwithin a region 480 having a minimum offset distance 482 from the vesselwall. The minimum offset distance 482 is provided by the smaller, secondeffective diameter 484 created by the helical lobes 454 in the offsetballoon segments 462. Thus, although the portions of the radiationsource 450 in the offset balloon segments 462 have more area of movementwithin the vessel 456 than the portion of the radiation source 450within the central balloon segment 460, they are constrained to theregion 480. The region 480 is maintained at the offset distance 482 sothat the radiation dose delivered to the vessel wall is equal to or lessthan a dosage determined by the minimum offset distance 482. Forexample, the second effective diameter 484 may be determined to providea minimum offset distance 482 from the vessel wall so that the radiationdose delivered to the vessel is 100 Gy or less at the vessel surface.Depending upon the radiation source, and the desired maximum radiationdose, the offset distance 482 may be varied by varying the secondeffective diameter 484. In this way, the offset balloon segments 462mitigate overdosing of the vessel by portions of the radiation source450 that extend beyond the therapeutic treatment length.

FIG. 20 illustrates an external side view of the stepped centeringcatheter of FIG. 17. In this embodiment, the stepped centering balloonsegment 444 may have a 32 mm length central balloon segment 460, 1 mmlength first steps 464, 5 mm length offset balloon segments 462, and 1mm length second steps 466.

In another embodiment, the stepped centering balloon segment 444 mayhave a 52 mm length central balloon segment 460, 1 mm length first steps464, 5 mm length offset balloon segments 462, and 1 mm length secondsteps 466.

It is to be understood that the above embodiments are only exemplary,and that other lengths may be used as necessitated by the length of thevessel to be treated and by the length of the portion of the radiationsource that is to be radially centered as well as the length of theportion to be offset. For example, in coronary applications, the lengthof the central balloon segment 460 may range from 12 mm to 90 mm. Thelength of the offset balloon segments 462 may range from 2 mm to 10 mm.In peripheral applications, the length of the central balloon segment460 may range from 5 cm to 20 cm. The length of the offset balloonsegments 462 may range from 2 mm to 15 mm. However, the above ranges areonly exemplary and the lengths will depend on the design of theradiation system and specific isotope used.

To enable utilization of the present invention within vessels ofdifferent diameters the above-described embodiments may be formed with avariety of first and second diameters (including effective diameters).The first and second diameters should be selected so that in combinationthe first diameter substantially centers a portion of the radiationsource within the lumen of the vessel along the therapeutic treatmentlength and the second diameter offsets portions of the radiation sourcethat extend beyond the central balloon segment 460 a minimum distancefrom the vessel wall. Additionally the minimum offset distance should bedetermined at a distance which mitigates overdosing a vessel. Forexample, in the following embodiments the second diameter may beselected to provide a minimum offset distance 482 of a ³²P radiationsource from the vessel so that the radiation dose is 100 Gy or less atthe surface of the vessel.

In one embodiment, when inflated, the central balloon segment 460 mayhave a 2.5 mm outer effective first diameter 470 and the offset balloonsegments 462 may have 1.75 mm outer effective second diameters 484.

In a second embodiment, when inflated, the central balloon segment 460may have a 3.0 mm outer effective first diameter 470 and the offsetballoon segments 462 may have 2.0 mm outer effective second diameters484.

In a third embodiment, when inflated, the central balloon segment 460may have a 3.5 mm outer effective first diameter 470 and the offsetballoon segments 462 may have 2.25 mm outer effective second diameters484.

In a fourth embodiment, when inflated, the central balloon segment 460may have a 4.0 mm outer effective first diameter 470 and the offsetballoon segments 462 may have 2.5 mm outer effective second diameters484.

It is to be understood that the above embodiments are exemplary and thatother diameters may be used. For example, in coronary applications theouter effective first diameter 470 may range in size from 2.0 mm to 4.0mm. The outer effective second diameters 484 may range from 1.5 mm to3.0 mm. In peripheral applications, the outer effective first diameter470 may range in size from 4.0 mm to 10 mm. The outer effective seconddiameters 484 may range from 2.0 mm to 7.0 mm. The above ranges are onlyexemplary and other diameters may be used dependent in large part uponthe isotope selected.

FIG. 21 illustrates a longitudinal cross-sectional view of anotherembodiment of a stepped centering catheter having a stepped centeringfluted balloon that may be used with present invention. In theembodiment of FIG. 21, the stepped centering catheter may be a steppedcentering fluted balloon catheter. The stepped centering fluted ballooncatheter 540 includes an elongate, tubular shaft 542 and a steppedcentering fluted balloon segment 544. The shaft 542 has a proximal endto allow introduction of a radioactive source 550, such as a radioactivesource wire, into the shaft lumen 548, and may have an open or closeddistal tip 546. The radioactive source 550 may have proximal and distalradio-opaque source markers 558 to enhance visualization by radioimagerysystems, such as fluoroscopy. The radio-opaque source markers 558 may beformed of tungsten, or of other materials, such as gold, or platinum.

The proximal end of the stepped centering fluted balloon catheter 540may be connected to a radiation source delivery device such as anafterloader, or other device, for advancing a radiation source withinthe stepped centering fluted balloon catheter 540. For example, anafterloader produced by Guidant Corporation, Houston, Tex., may be used.If an afterloader is used in conjunction with the present invention, thestepped centering fluted balloon catheter 540 may be connected to theafterloader system utilizing a key connector that allows the afterloadersystem to identify the particular characteristics of the steppedcentering catheter.

As illustrated in FIG. 21, the stepped centering fluted balloon segment544 may be formed as a continuous, inflatable fluted balloon including aplurality of individual fluted lobes 554 spaced around the shaft 542. Aninflation lumen may be provided at the proximal end of the steppedcentering fluted balloon segment 544 to allow inflation from a pump orother inflation apparatus.

The stepped centering fluted balloon segment 544 may include a centralfluted balloon segment 560 of a first diameter and offset fluted balloonsegments 562 of a smaller, second diameter. It is to be noted that wheninflated, the nature of a fluted balloon is such that together theindividual fluted lobes 554 create an effective diameter which limitsthe radial positioning of the radiation source 550 within the vessel556.

The stepped centering fluted balloon catheter 540 may have proximal anddistal radio-opaque markers 552A and 552B attached to the shaft 542 thatdelineate the proximal and distal ends of the central fluted balloonsegment 560. In this way, the markers 552A and 552B delineate theportion of the radiation source 550 that is substantially centeredwithin the vessel lumen.

In use, the stepped centering fluted balloon catheter 540 is selected sothat when properly inflated, the first effective diameter of the centralfluted balloon segment 560 is sized to be just large enough tocompliantly engage the walls of vessel 556 and to substantially centerthe shaft lumen 548, and, thus, a portion of the radiation source 550,within the lumen of the vessel 556. For example, the first effectivediameter of the central fluted balloon segment 560 may be determined tosubstantially center a portion of the radiation source 550 which maydeliver a therapeutic dose of 20 Gy at 1 mm into the vessel. The firsteffective diameter of the central fluted balloon segment 560 is steppeddown to the smaller, second effective diameter of the offset flutedballoon segments 562 across first steps 564. In this example, the firsteffective diameter of the central fluted balloon segment 560 iscontinued to the interior edges of the markers 552A and 552B, i.e., thetherapeutic treatment length. Thus, the central fluted balloon segment560 substantially centers the therapeutic dose region of radiationsource 550 between the markers 552A and 552B. The first effectivediameter is then gradually tapered to the second effective diameteralong the length of the first steps 564.

The second effective diameter of the offset fluted balloon segments 562is sized to offset portions of the radiation source 550 which extendbeyond the central fluted balloon segment 560 within a region having aminimum offset distance from the vessel wall. In this way, the radiationdose delivered to the vessel wall from the portions of the radiationsource 550 that extend beyond the central fluted balloon segment 560 maybe controlled to prevent overdosing the vessel. For example, the secondeffective diameters of the offset fluted balloon segments 562 may bedetermined to limit the radiation dose delivered by the portions of theradiation source 550 which extend beyond the central fluted balloonsegment 560, as discussed above, to 100 Gy or less at the vesselsurface. Thus, the offset fluted balloon segments 562 offsetsub-therapeutic portions of the radiation source 550 that extend outsidethe markers 552A and 552B to prevent overdosing the vessel.Additionally, although the offset fluted balloon segments 562 may extendbeyond the therapeutic treatment length of the vessel, the smaller,second effective diameter should not cause or exacerbate stretches ortears in the vessel, thus mitigating further damage to the vessel.

It is to be noted that although the present embodiment is shown havingoffset fluted balloon segments 562 both proximal and distal to thecentral fluted balloon segment 560, alternative embodiments may haveonly a proximal offset fluted balloon segment 562 or a distal offsetfluted balloon segment 562 with the corresponding first and secondsteps. In these embodiments, the opposite side of the central flutedballoon segment 560 without an offset fluted balloon segment 562 mayretain a first step 564 tapering the first effective diameter to thediameter of the shaft 542. In other embodiments, the diameter of theshaft 542 may be sufficiently similar to the first effective diameter sothat the opposite side of the central fluted balloon segment 560 withoutan offset fluted balloon segment 562 may not require a first step 564.

The second effective diameter of the offset fluted balloon segments 562is stepped down to the smaller diameter of the shaft 542 across secondsteps 566. In this example, the second effective diameter of the offsetfluted balloon segments 562 is continued to the end of the radiationsource 550. The second effective diameter is then gradually tapered tothe diameter of the shaft 542 along the length of the second steps 566.The first steps 564 and second steps 566 allow for a gradual increaseand reduction in the effective diameters created by the fluted lobes 554as the stepped centering fluted balloon catheter 540 is positionedwithin the vessel. The gradual tapering is provided to allow the vesselwalls to gradually respond to the differences in diameters of thecentering fluted balloon catheter 540 structure in an attempt tomitigate additional damage to the vessel.

The stepped centering fluted balloon segment 544 may be fabricated usingstandard techniques well known to those of ordinary skill in the art. Inone embodiment, the stepped centering fluted balloon segment 544 may befabricated using a shape mold and materials of relatively high strengththat will expand to a fixed diameter when inflated, such as relativelyhigh strength polymers, i.e., nylon, polyester, or polyvinyl acetate orpolyethylene. The stepped centering fluted balloon segment 544 isattached to the shaft 542 by bonds that are located at the ends of thestepped centering fluted balloon segment 544. The bonds may be thermalor ultrasonic welds, adhesive or solvent bonds, or may be formed byother conventional means well known to those of ordinary skill in theart.

The radio-opaque markers 552A and 552B may be gold, platinum, or othermaterials commonly viewable using radioimagery systems, such asfluoroscopy. The radio-opaque markers 552A and 552B may be attached tothe shaft 542 by conventional means well known to those of ordinaryskill in the art. In one embodiment, the radio-opaque markers 552A and552B may be attached to the shaft 542 immediately outside the centralfluted balloon segment 560 to delineate the endpoints of the centralfluted balloon segment 560. It will be appreciated that when used withthe present invention, the length of the central fluted balloon segment560 may be determined according to the therapeutic treatment lengthcalculated for a particular vessel. In this way, using radioimagerysystems, the radio-opaque markers 552A and 552B provide a visuallandmark of the portion of the radioactive source 550 that issubstantially centered within the vessel.

Thus, there has been described several embodiments of a steppedcentering balloon which may be used with the present invention fordelivery of intravascular radiation therapy in which a portion of aradiation source is substantially centered within the lumen of a vesselalong a therapeutic treatment length and portions of the radiationsource that extend outside the therapeutic treatment length areconstrained within a region that has a minimum offset from the vesselwall.

In one embodiment, the stepped centering balloon includes a centralballoon segment of a first effective diameter continuous with smalleroffset balloon segments of a second effective diameter located to eachside of the central balloon segment. The first effective diameter of thecentral balloon segment is reduced to the smaller, second effectivediameters of the offset balloon segments across first steps, and thesecond effective diameters of the offset balloon segments are reduced tothe shaft diameter of the catheter across second steps.

The first effective diameter substantially centers a portion of aradiation source within a vessel so that a therapeutic dose of radiationmay be delivered along a therapeutic treatment length. The secondeffective diameter constrains portions of a radiation source thatextends outside the therapeutic treatment length within a region havinga minimum offset from the vessel wall. The first and second stepsprovide a tapered transition between the different balloon segmentdiameters and the shaft diameter to mitigate further damage to vesseloutside the therapeutic treatment length.

In alternative embodiments, a single offset balloon adjacent to eitherthe proximal or distal end of the central balloon segment may beutilized. In these alternative embodiments, the first effective diameterof the central balloon segment is reduced to the effective diameter ofthe offset balloon segment across a first step, and the second effectivediameter of the offset balloon segment is reduced to the shaft diameteracross a second step. The opposite side of the central balloon segmentmay either be reduced to the shaft diameter across a first step, or maynot require a reduction due to the size of the shaft diameter.

It is to be understood that the radio-opaque markers and markermaterials discussed with reference to the above examples are merely forillustration, and that other markers, fewer or no markers, and othermarker materials may be used. It is to be further understood that whenradio-opaque markers are discussed herein, the markers may be other thanradio-opaque if viewable using a radioimagery system. Additionally,although the stepped centering balloon catheter was discussed withreference to a ³²P radiation source, it is to be understood thatradiation sources other than ³²P may be used and that modification ofthe first and second diameters and minimum offset distances may berequired. For example, radiation sources may utilize different isotopesand geometries in addition to those described herein.

Thus, the present invention as described includes methods andapparatuses for positioning a radiation source in vivo relative toradio-opaque markers on a catheter that delineate a therapeutictreatment length, so that a therapeutic dose of radiation is deliveredalong the therapeutic treatment length.

In one embodiment, the present invention includes a method fordetermining a total radiation source length necessary to deliver atherapeutic dose of radiation along a therapeutic length.

The present invention further includes methods and devices that visuallyindicate the therapeutic treatment length utilizing markers, and allow aradiation source to be positioned relative to the markers so that atherapeutic dose is delivered along the therapeutic treatment length.These methods and devices allow the therapeutic dose of radiation to bedelivered using a single radiation source length equal to the totalradiation source length, or by using a radiation source length accordingto a stepping protocol that creates an effective total radiation sourcelength.

In one embodiment, the present invention includes methods and devicesfor positioning an active source wire relative to the positioning of adummy source wire, where the dummy source wire was initially positionedrelative to proximal and a distal catheter markers that defined atherapeutic treatment length.

It is to be understood that the various methods and apparatusesdescribed herein are not limited to stepped centering balloon catheters,and may be used with other centering catheters as well as non-centeringcatheters. However, the use of other catheters may result in delivery ofradiation doses which differ from those described herein.

Further, although a therapeutic dose of radiation may be defined as atleast the minimum amount of radiation that will effectively reducerestenosis when delivered to a prescribed location of a vessel, it is tobe understood that a therapeutic dose of radiation may be defined atother levels determined for a particular radiotherapy treatment.

It is also to be understood that the markers although described asradio-opaque, need only be visible utilizing a radioimagery system usedin the procedure and that the particular examples discussed herein aremerely for illustration and that other materials may be used.

Additionally, it is to be understood that although the radiation sourcesdescribed herein are described as having proximal and distalsub-therapeutic dose regions and a therapeutic dose region in between,other radiation sources that have only one of the sub-therapeutic doseregions in addition to the therapeutic dose region may be used. In thesecases the methods and apparatuses described herein would be usedaccordingly and may require some modification.

In the foregoing specification, the invention has been described withreference to specific exemplary embodiments thereof. It will, however,be evident that various modifications and changes may be made theretowithout departing from the broader spirit and scope of the invention asset forth in the appended claims. The specification and drawings are,accordingly, to be regarded in an illustrative rather than a restrictivesense.

We claim:
 1. A radiation delivery catheter comprising: an elongate,tubular member having a lumen for receiving a radiation source; ahelical balloon disposed around said elongate, tubular member; andproximal and distal markers attached to said elongate, tubular member,wherein said proximal and distal markers are spaced apart along saidelongate, tubular member so as to define a therapeutic treatment length.2. The catheter of claim 1 wherein said elongate, tubular membersubstantially radially centers said therapeutic treatment length withina vessel lumen.
 3. The catheter of claim 1 wherein said helical balloonsubstantially radially centers said therapeutic treatment length withina vessel lumen.
 4. The catheter of claim 1 further comprising acentering balloon that substantially radially centers said therapeutictreatment length within a vessel lumen.
 5. The catheter of claim 1wherein said therapeutic treatment length is the region in which atherapeutic dose of radiation is delivered.
 6. The catheter of claim 5wherein a therapeutic dose of radiation is at least the minimum amountof radiation that will effectively reduce restenosis when delivered to aprescribed location of vessel.
 7. The catheter of claim 1, wherein saiddistal marker is spaced a distance proximal to a position of said lumen,said distance being at least a distal length of said radiation source inwhich a sub-therapeutic dose of radiation is delivered.
 8. A radiationdelivery catheter comprising: an elongate, tubular member having adead-end lumen for receiving a radiation source; a proximal marker and adistal marker attached to said elongate, tubular member, wherein saidproximal and distal markers are spaced apart along said elongate,tubular member so as to define a therapeutic treatment length, saiddistal marker being spaced a distance proximal to said dead-end lumen,said distance being at least the distal length of the radiation sourcein which a sub-therapeutic dose of radiation is delivered.
 9. Thecatheter of claim 8 wherein said distance further includes a lengthdefined by one or more positioning tolerances.
 10. The catheter of claim8 wherein said elongate, tubular member substantially radially centerssaid therapeutic treatment length within a vessel lumen.
 11. Thecatheter of claim 8 further comprising a centering mechanism thatsubstantially radially centers said therapeutic treatment length withina vessel lumen.
 12. The catheter of claim 8 further comprising acentering balloon that substantially radially centers said therapeutictreatment length within a vessel lumen.